22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ–LXRα–ABCA1 pathway in cholesterosis of the gallbladder

Wang, Jingmin; Wang, Dong; Tan, Yu-Yan; Zhao, Gang; Ji, Zhenling

doi:10.1016/j.bbrc.2014.03.130

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…PPARγ2, which mainly exists in adipose tissue, plays an important role in the differentiation of adipocytes. Inhibition of PPARγ2 expression prevents adipocyte differentiation (Taher et al, 2015; Wang, Wang, Tan, Zhao, & Ji, 2014). Therefore, we tried to study whether IL‐38 can affect the expression of PPARγ2 and other transcription factors during adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Chen

Sun

et al. 2020

Cell Biology International

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Interleukin-38 (IL-38) is a novel member of the IL-1 cytokine family with anti-inflammatory activity. However, its effect on adipogenesis and inflammatory cytokines secretion of adipocytes in vitro has not been reported. To address whether IL-38 inhibits adipogenesis and inflammation in vitro, adipose precursor 3T3-L1 cells were cultured with or without IL-38. The morphology and size of lipid droplets in 3T3-L1 cells were measured by Oil red O staining. The mRNA expression levels of GATA-binding protein-3 (GATA-3), glucose transporter type 4 (GLUT4), peroxisome proliferator-associated receptor γ2, IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 cells were detected by real-time PCR, The contents of IL-6, IL-1β, and MCP-1 in 3T3-L1 cell medium supernatants were determined by enzyme-linked immunosorbent assay. IL-38 significantly decreased the number of lipid droplets in 3T3-L1 cells. IL-38 also increased GATA-3 and GLUT4 mRNA expression and inhibited IL-1β, IL-6, and MCP-1 secretion by 3T3-L1 cells. It is concluded that IL-38 can inhibit the differentiation of human adipocytes and inflammatory cytokine production by 3T3-L1 cells.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Chen

Sun

et al. 2020

Cell Biology International

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“…Additionally, cholesterol efflux, as the initial step of cholesterol reversal transport, is one of the important mechanisms of anti‐atherosclerosis (Nakaya et al., ). Existing evidences have showed that the expressions of PPAR‐γ, LXRα, as well as ABCA1 are related to cholesterol efflux (Wang, Wang, Tan, Zhao, & Ji, ; Wang & Tontonoz, ). LXRα, as a subgroup of PPAR‐γ, regulates cholesterol homoeostasis through upregulating ABCA1 expression, which then stimulates cholesterol efflux from cells to plasma lipid‐free Apo‐A1 (Chinetti et al., ; Wade & Owen, ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Genistein on Cholesterol Metabolism‐Related Genes in HepG2 Cell

Zheng

Yin

et al. 2019

Journal of Food Science

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It has been reported that genistein could improve metabolic syndromes. Our study aimed to investigate the effects and potential mechanisms of genistein on improving cholesterol metabolism in HepG2 cell. HepG2 cells were cultured with 0, 0.01, 1.00, 10.00, and 50.00 µM genistein for 24 hr. The current results showed a dose‐dependent manner between genistein and intracellular contents of total cholesterol (TC), high‐density lipoprotein‐cholesterol (HDL‐C), and cellular apolipoprotein A1 (Apo‐A1) secretion. TC was increased by 25.69%, meanwhile HDL‐C and Apo‐A1 were decreased by 56.00% and 25.93%, respectively, when the dosage of genistein was 1.00 µM. Genistein dose‐dependently upregulated the protein and mRNA levels of sterol regulatory element binding proteins‐2 (SREBP‐2), as well as the mRNA levels of low‐density lipoprotein receptor (LDLR) and 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase (HMGCR), by 145.91%, 72.29%, 310.23%, and 123.08%, respectively, when we gave 1.00 µM genistein, indicating that intracellular cholesterol synthesis and absorption of exogenous cholesterol were increased. In addition, the mRNA levels of peroxisome proliferator‐activated receptor‐γ (PPARγ) and liver X receptor (LXRα), lowered by 58.23% and 34.86% at 0.01 µM genistein, were reduced in a dose‐dependent manner. LXRα and ATP‐binding cassette transporter A1 (ABCA1) protein levels were significantly (P < 0.05) decreased by 50.35% and 11.60% at 1.00 µM genistein, which indicated that cellular cholesterol efflux was inhibited. Taken together, our results suggested that genistein at dosage of more than 1.00 µM was able to increase the intracellular cholesterol levels by up regulating SREBP‐2/LDLR/HMGCR pathway and suppressing PPARγ/LXRα/ABCA1 pathway. Practical Application In this study, genistein appeared to be effective in reducing plasma cholesterol levels due to increase the intracellular cholesterol levels by upregulating cholesterol absorption through SREBP‐2/LDLR/HMGCR pathway, and also downregulating cholesterol efflux via PPARγ/LXRα/ABCA1 pathway in vitro. In addition, plasma cholesterol is regarded as the key indicator of atherosclerosis; therefore, we believe that our findings could be used for further exploration on a possible therapeutic application of genistein for atherosclerosis.

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“…Thiazolidinediones are probably the most well-known and widely used PPARg agonists, due to their antidiabetic properties. Thiazolidinediones, including pioglitazone, ciglitazone, and rosiglitazone, enhanced LXRa expression, which subsequently induced ABCA1 protein expression and cholesterol efflux toward apoA-I in vitro (Chawla et al, 2001;Chinetti et al, 2001;Claudel et al, 2001;Cabrero et al, 2003;Li et al, , 2015Llaverias et al, 2006;Panzenboeck et al, 2006;Nakaya et al, 2007;Lee et al, 2008;Tanabe et al, 2008;Ogata et al, 2009;Cocks et al, 2010;Ozasa et al, 2011;Wang et al, 2014bWang et al, , 2015bJiang and Li, 2017) (Table 2). Contradictory to these results with pioglitazone in THP-1 macrophages and J774 macrophages, an attenuated or unaffected ABCA1 expression was found in peritoneal macrophages isolated from 15PGJ2-, troglitazone-, and pioglitazonetreated C57BL/6 mice, and in the liver of pioglitazonetreated LDLR 2/2 C57BL/6 mice (Ruan et al, 2003;Ogata et al, 2009;Ozasa et al, 2011;Zhao et al, 2015;Jiang and Li, 2017;Silva et al, 2018).…”

Section: B Liver X Receptor Activation To Induce Atp-binding Cassette A1 and Atp-binding Cassette G1 Expressionmentioning

confidence: 99%

Brothers in Arms: ABCA1- and ABCG1-Mediated Cholesterol Efflux as Promising Targets in Cardiovascular Disease Treatment

et al. 2019

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Atherosclerosis is a leading cause of cardiovascular disease worldwide, and hypercholesterolemia is a major risk factor. Preventive treatments mainly focus on the effective reduction of low-density lipoprotein cholesterol, but their therapeutic value is limited by the inability to completely normalize atherosclerotic risk, probably due to the disease complexity and multifactorial pathogenesis. Consequently, high-density lipoprotein cholesterol gained much interest, as it appeared to be cardioprotective due to its major role in reverse cholesterol transport (RCT). RCT facilitates removal of cholesterol from peripheral tissues, including atherosclerotic plaques, and its subsequent hepatic clearance into bile. Therefore, RCT is expected to limit plaque formation and progression. Cellular cholesterol efflux is initiated and propagated by the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Their expression and function are expected to be rate-limiting for cholesterol efflux, which makes them interesting targets to stimulate RCT and lower atherosclerotic risk. This systematic review discusses the molecular mechanisms relevant for RCT and ABCA1 and ABCG1 function, followed by a critical overview of potential pharmacological strategies with small molecules to enhance cellular cholesterol efflux and RCT. These strategies include regulation of ABCA1 and ABCG1 expression, degradation, and mRNA stability. Various small molecules have been demonstrated to increase RCT, but the underlying mechanisms are often not completely understood and are rather unspecific, potentially causing adverse effects. Better understanding of these mechanisms could enable the development of safer drugs to increase RCT and provide more insight into its relation with atherosclerotic risk.Significance Statement--Hypercholesterolemia is an important risk factor of atherosclerosis, which is a leading pathological mechanism underlying cardiovascular disease. Cholesterol is removed from atherosclerotic plaques and subsequently cleared by the liver into bile. This transport is mediated by high-density lipoprotein particles, to which cholesterol is transferred via ATP-binding cassette transporters ABCA1 and ABCG1. Small-molecule pharmacological strategies stimulating these transporters may provide promising options for cardiovascular disease treatment.

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22(R)-hydroxycholesterol and pioglitazone synergistically decrease cholesterol ester via the PPARγ–LXRα–ABCA1 pathway in cholesterosis of the gallbladder

Cited by 9 publications

References 20 publications

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Effect of Genistein on Cholesterol Metabolism‐Related Genes in HepG2 Cell

Brothers in Arms: ABCA1- and ABCG1-Mediated Cholesterol Efflux as Promising Targets in Cardiovascular Disease Treatment

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